The present invention relates to a pharmaceutical composition for reducing vaginal acidity, treating abnormal enhancement of vaginal acidity, and high acidity vaginitis associated with abnormal enhancement of vaginal acidity, especially for the treatment of fungal vaginitis, comprising of one or more ingredients defined as follows: amino acids, physiologically acceptable salts of amino acids, oligopeptides and polypeptides. Also, the present invention relates to the use of the said amino acids, physiologically acceptable salts of amino acids, oligopeptides and polypeptides, as active ingredients or auxiliaries in preparing drugs for reducing vaginal acidity, the treatment of abnormal enhancement of vaginal acidity, and high acidity vaginitis especially to their use in preparing drugs for the treatment of fungal vaginitis and the use thereof as nutrients for vaginal mucous membranes in preparing drugs that are locally applied in the vagina It also relates to methods for reducing vaginal acidity, treatment of abnormal enhancement of vaginal acidity, and high acidity vaginitis associated with abnormal enhancement of vaginal acidity, and especially for treatment of fungal vaginitis.
Fungal vaginitis, one of the common female vaginal diseases with a high morbidity rate, is difficult to effect a radical cure. In the U.S., more than 75% women suffer from fungal vaginitis at least once in their life, and about 5% of adult women suffer from repeated fungal vaginal infection, which is difficult to treat (Jack D. Sobel, MD. Candidal Vulvovaginitis, Clinical Obstetrics and Gynecology, 1993 Vol.36 (1): 153-165). The main clinical symptoms of these vaginal diseases include vulval pruritus, vaginal pain, leukorrhagia, dyspareunia, and urodynia. Therefore, this disease is harmful to the health of women as well as their life quality.
At present, for the treatment of fungal vaginitis, there are various anti-fungal drugs used to directly inhibit or kill fungi. The commonly used drugs include Ketoconazole, Fluconazole, mikostatin and Clotrimazolum, they can be administered locally in the vagina or taken orally. But most of the local vaginal anti-fungal agents contain starch and/or lactose as auxiliaries, for example as excipient. The present inventor has discovered that starch, lactose or other saccharides can significantly promote vaginal bacteria to produce acid, increase vaginal acidity, thus promoting fungal growth in the vagina, therefore the starch and/or lactose contained in the pharmaceutical composition is extremely unfavorable for the treatment of fungal infection in the vagina.
Currently, satisfactory effects cannot be achieved if sole anti-fungal drugs are used for the treatment of these vaginal diseases. For example, the treatment effect of the commonly used drugs such as, mikostatin, is generally 75-80%. A better effect can be achieved if glyoxaline anti-fungal drugs such as Ketoconazole, Treconazole, and Fluconazole, are used, which equates to about 85-90% (Jack D.Sobel). However, for many patients, the disease is often repeated after stopping the administration of the drug or during the next menstrual period, which makes it very difficult to effect any radical cure.
The object of the present invention is to provide a medicine for reducing vaginal acidity, treatment for abnormal enhancement of vaginal acidity, high acidity vaginitis and fungal vaginitis. This invention also relates to methods for treatment of abnormal enhancement of vaginal acidity, and high acidity vaginitis, especially for treatment of fungal vaginitis.
In order to seek a medicine which is effective in treating fungal vaginitis, the inventor conducted an extensive study, resulting in a simple formulation, which is easily used and applied. Utilizing Light Microscopy techniques, the inventor performed observations on vaginal secretions obtained from patients with fungal vulvovaginitis according to clinical diagnosis. It is difficult to determine the direct relationship between the clinical symptoms and fungal infection, because the inventor did not find fungi in the vaginal secretions in many of the patients examined. After further study however, the inventor achieved surprising resultsxe2x80x94for these cases the acidity in the vagina was abnormally higher (vaginal pH value  less than 4.0) and a single case of high acidity can cause damage to vaginal mucous membranes, resulting in vaginitis. This therefore confirms that these cases actually relate more directly to abnormal enhancement of acidity in the vagina. The inventor calls these cases xe2x80x9chigh acidity vaginitisxe2x80x9d. The inventor also noticed that xe2x80x9chigh acidity vaginitisxe2x80x9d has a close relationship with fungal vulvovaginitis, fungal vaginitis are accompanied with high acidity vaginitis. This is one of the main reasons why it is difficult to effect a radical cure for the repeated and stubborn fungal vaginitis by using only anti-fungal drugs. This discovery is of great significance because the inventor has set forth a new theory for the treatment of fungal vaginitis: namely, treatment for repeated and stubborn fungal vaginitis and correcting abnormal enhancement of vaginal acidity. This discovery is as important as the treatment with anti-fungal drugs, which will play an important role in raising the effect of the treatment for fungal vaginitis. The inventor corrected the abnormally-enhanced vaginal acidity and the diagnosed cases of fungal vaginitis by only using the medicine of the present invention, whereas any other anti-fungal drugs were not used. After treatment with the invention which involved correction of an abnormally-high acid environment in the vagina, the fungal infection disappeared, which is unimaginable before.
Clinically, sodium bicarbonate is used to clean the vagina to perform auxiliary treatment for fungal vaginitis. However, the mechanism of sodium bicarbonate solution has been commonly thought to change the micro-environment in the vagina and inhibit the growth of fungi. This is not the case that sodium bicarbonate solution changes the microenvironment in the vagina and inhibits the growth of fungi, as commonly known, but is that it decreases vaginal acidity temporarily. This method cannot reduce the acidity in the vagina and the treatment effect lasts for a short time, therefore, there is high acidity again in the vagina several hours after stopping the use of drugs.
The U.S. Pat. No. 4,804,674 teaches a method for enhancing sperm motility, wherein amino acids and/or salts of amino acids are used which can enhance sperm motility. These amino acids arc mainly comprising aspartic acid, glutamic acid, arginine, histidine, asparagine, glutamine, and arginine aspartate. This patent does not indicate that the amino acids, oligopeptide and polypeptide can regulate vaginal bacterial metabolism, thus reducing the acid production in the vagina, nor does it indicate that vaginal acidity can be reduced by regulating vaginal bacterial metabolism. Also, the patent does not mention the relationship between abnormal enhancement of vaginal acidity and fungal vaginitis, or that amino acids, oligopeptide and polypeptide are used for reducing abnormal enhancement of vaginal acidity, treatment of high acidity vaginitis and fungal vaginitis.
The U.S. Pat. No. 4,937,234 discloses a pharmaceutical composition of neutral salts of gluconic acid, wherein zinc gluconate is an effective bacteriological component. Such amino acids as alanine, valine, isoleucine, proline, glycine, serine, threonine, asparagine, glutamine, lysine, arginine, histidine and mixtures thereof are also used as auxiliaries in the pharmaceutical composition of this patent, of which the main component is lysine. As shown in the examples 1 to 12 of the patent specification, the patent emphasizes that amino acids can regulate and change the acidity of the composition to neutral, and thus reduces the stimulation of the composition and enhances the sterilization of zine agents. This patent particularly emphasizes that its pharmaceutical composition can be used on the neonates, old people, eyes and noses that are sensitive to acid, for treatment of diaper rash, skin dryness and vaginitis. Although the patent mentions that the composition can treat vaginitis, it does not indicate what type of vaginitis the composition can treat, because completely different treatment methods and drugs are used for different types of vaginitis. Furthermore, no information or data indicates or suggests whether the lysine also exerts treatment effect on vaginitis when used separately. The inventor discovered that lysine is easily converted into toxic cadaverine in the vagina through bacterial metabolism, thus it is not suitable to administer lysine in a large amount into the vagina, particularly, it cannot be administered alone into the vagina, This patent does not indicate that the amino acids, oligopeptide and polypeptide can regulate vaginal bacterial metabolism thus reducing the acid production in the vagina, nor does it indicate that vaginal acidity can be reduced by regulating vaginal bacterial metabolism. Also, the patent does not mention the relationship between abnormal enhancement of vaginal acidity and fungal vaginitis, or that amino acids, oligopeptide and polypeptide are used for reducing abnormal enhancement of vaginal acidity, treatment of high acidity vaginitis and fungal vaginitis.